Cell Type-Specific Roles of STAT3 Signaling in the Pathogenesis and Progression of K-ras Mutant Lung Adenocarcinoma

Authors

Michael J Clowers
Seyed Javad Moghaddam

Publication Date

3-31-2022

Journal

Cancers

Abstract

Worldwide, lung cancer, particularly K-ras mutant lung adenocarcinoma (KM-LUAD), is the leading cause of cancer mortality because of its high incidence and low cure rate. To treat and prevent KM-LUAD, there is an urgent unmet need for alternative strategies targeting downstream effectors of K-ras and/or its cooperating pathways. Tumor-promoting inflammation, an enabling hallmark of cancer, strongly participates in the development and progression of KM-LUAD. However, our knowledge of the dynamic inflammatory mechanisms, immunomodulatory pathways, and cell-specific molecular signals mediating K-ras-induced lung tumorigenesis is substantially deficient. Nevertheless, within this signaling complexity, an inflammatory pathway is emerging as a druggable target: signal transducer and activator of transcription 3 (STAT3). Here, we review the cell type-specific functions of STAT3 in the pathogenesis and progression of KM-LUAD that could serve as a new target for personalized preventive and therapeutic intervention for this intractable form of lung cancer.

Keywords

STAT3, lung adenocarcinoma, TME, K-ras, tumor-promoting inflammation, mucosal immunology, myeloid

DOI

10.3390/cancers14071785

PMID

35406557

PMCID

PMC8997152

PubMedCentral® Posted Date

3-31-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes